Probing vaccine antigens against bovine mastitis caused by Streptococcus uberis

Publication date: Available online 6 June 2016
Source:Vaccine
Author(s): Rosa Collado, Antoni Prenafeta, Luis González-González, Josep Antoni Pérez-Pons, Marta Sitjà
Streptococcus uberis is a worldwide pathogen that causes intramammary infections in dairy cattle. Because virulence factors determining the pathogenicity of S. uberis have not been clearly identified so far, a commercial vaccine is not yet available. Different S. uberis strains have the ability to form biofilm in vitro, although the association of this kind of growth with the development of mastitis is unknown. The objective of this study was to evaluate the potential use as vaccine antigens of proteins from S. uberis biofilms, previously identified by proteomic and immunological analyses. The capability of eliciting a protective immune response by targeted candidates was assayed on a murine model. Sera from rabbits immunized with S. uberis biofilm preparations and a convalescent cow intra-mammary infected with S. uberis were probed against cell wall proteins from biofilm and planktonic cells previously separated by two-dimensional gel electrophoresis. Using rabbit immunized serum, two proteins were found to be up-regulated in biofilm cells as compared to planktonic cells; when serum from the convalescent cow was used, up to sixteen biofilm proteins were detected. From these proteins, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fructose-biphosphate aldolase (FBA), and elongation factor Ts (EFTs) were chosen to be tested as vaccine antigen candidates. For this purpose, different groups of mice were immunized with the three recombinant-expressed proteins (each one formulated separately in a vaccine), and thereafter intraperitoneally challenged with S. uberis. The three proteins induced specific IgG antibodies, but a significant reduction of mortality was only observed in the groups of mice vaccinated with FBA or EFTs. These results suggest that FBA and EFTs might be considered as strong antigenic candidates for a vaccine against S. uberis bovine mastitis. Moreover, this is the first study to indicate that also in S. uberis, GAPDH, FBA and EFTs, as proteins detected in both cytoplasm and cell wall fractions, can play a second function (moonlighting), the latter being particularly involved in the virulence of such a pathogen organism.



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IGF1R and c-met as therapeutic targets for colorectal cancer

Publication date: August 2016
Source:Biomedicine & Pharmacotherapy, Volume 82
Author(s): Hajar Shali, Majid Ahmadi, Hossein Samadi Kafil, Abbasali Dorosti, Mehdi Yousefi
The type 1 IGF receptor (IGF1R) and mesenchymal-epithelial transition (MET) are hetrodimeric and transmembrane receptor tyrosine kinases, which are frequently overexpressed by several tumor types, including colorectal cancer (CRC). These receptors bind to their specific ligands, insulin growth factors (IGFs) and hepatocyte growth factor (HGF), respectively, and promote signaling cascades which mediates many functions such as proliferation and protection against apoptosis, cell scattering, tumor cell motility, invasion and metastasis. In patients with metastatic colorectal cancer (mCRC), IGF1R and c-met expression confer resistance to cetuximab (monoclonal antibodies against EGFR). Therefore, the c-met and IGF1R are now an attractive novel target for anticancer therapy. In this review, we will describe correlation between two receptors and their activation effects in tumor cells, and finally introduce useful and available strategies for their targeting.



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Role of β-Adrenoceptors and L-Type Ca 2+ -Channels in the Mechanism of Reperfusion-Induced Heart Injury

We studied the effects of β-adrenoceptor antagonists propranolol and nadolol and L-type Ca²⁺-channel blocker verapamil on cardiac reperfusion injury developed after 45-min coronary occlusion. The substances were injected intravenously 5 min before reperfusion. The results indicate that activation of β-adrenoceptors and opening of L-type Ca²⁺-channels promote the development of cardiac reperfusion injury, while blockage of β-adrenoceptors and/or L-type Ca²⁺-channels prevents reoxygenation-induced myocardial injury. Propranolol, nadolol, and verapamil can produce infraction-limiting effects after onset of ischemic heart injury.

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Anxiolytic, Psychostimulant, and Analgesic Effects of Various Volumes of Ethanol Solution in Different Concentrations, but in the Same Dose

We studied the effect of ethanol (dose 2 g/kg) in various concentrations (5, 13, and 40%) and different volumes (40, 15.5, and 5 ml/kg) on the level of anxiety, locomotor activity, and pain sensitivity in rats. Administration of 40 ml/kg water to animals was followed by a significant increase in the time spent in the open arms of the elevated plus maze. Administration of water in a volume of 5 or 15.5 ml/kg had little effect on the level of anxiety. The greater was the volume of intragastrically administered ethanol, the stronger was the anxiolytic effect. The psychostimulant and analgesic effects of ethanol were more pronounced after administration of medium volumes and intermediate concentrations of ethanol-containing solutions. Since administration of these solutions cannot produce maximum blood concentration of ethanol, we believe that the observed effects are mainly related to the direct effect of ethanol on the stomach tissue.

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New Genetic Constructs for Generation of Stable Therapeutic Antibodies to Organophosphorus Toxins in Methylotrophic Yeasts Pichia Pastoris

We propose a new method of obtaining of stable Fab-fragments of antibodies in Pichia pastoris expression system. Recently, we obtained Fab-fragments of antibodies neutralizing organophosphorus toxins. However, high yield of the target products was not attained because of high level of proteolytic degradation. In the present study, we identified sites of proteolytic degradation in Fab-fragments and endogenous proteases performing degradation, which allowed obtaining optimized genetic constructs for expression of antibody heavy chains (IgGγ1) and kappa and lambda isotypes of light chains. Co-transformation of these vectors allowed obtaining Fab-fragments of antibodies to organophosphorus toxins without proteolytic degradation of the product.

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Ketamine-Midazolam Anesthesia Induces Total Inhibition of Cortical Activity in the Brain of Newborn Rats

The effects of general anesthetics ketamine and midazolam, the drugs that cause neuroapoptosis at the early stages of CNS development, on electrical activity of the somatosensory cortex in newborn rats were studied using extracellular recording of local field potentials and action potentials of cortical neurons. Combined administration of ketamine (40 mg/kg) and midazolam (9 mg/kg) induced surgical coma and almost completely suppressed early oscillatory patterns and neuronal firing. These effects persisted over 3 h after injection of the anesthetics. We concluded that general anesthesia induced by combined administration of ketamine and midazolam profoundly suppressed cortical activity in newborn rats, which can trigger neuroapoptosis in the developing brain.

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Peptidyl Aldehyde Specifically Interacts with Immunosubunit β1i Proteasome: In Vitro and In Vivo Effects

We studied the effect of β1i-specific peptidyl aldehyde IPSI-001 on proteasome from mammalian cells. In concentrations <1 μM, this agent effectively suppressed immunoproteasome, but only slightly reduced chymotrypsin-like activity of constitutive proteasome. Intraperitoneal administration of this inhibitor to C3H/He mice in a dose of 100 mg/kg induced no significant physiological or behavioral changes, which attested to its considerable therapeutic potential in the treatment of autoimmune neurodegenerative pathologies.

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